caa a22 4500 605507260 CHVBK 20210128100631.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00775-015-1240-z doi (NATIONALLICENCE)springer-10.1007/s00775-015-1240-z Theoretical insights into the mechanism of redox switch in heat shock protein Hsp33 [Elektronische Daten] [Mironel Enescu, Rima Kassim, Christophe Ramseyer, Bruno Cardey] Heat shock protein 33 (Hsp33) is activated in the presence of H2O2 by a very interesting redox switch based on a tetra-coordinated zinc-cysteine complex present in the fully reduced and inactive protein form. The oxidation of this zinc center by H2O2 induces formation of two S-S bridges and the zinc release followed by the protein unfolding. We report here a theoretical study of the step-by-step sequence of the overall process starting with the oxidation of the first cysteine residue and ending with the zinc release. Each reaction step is characterized by its Gibbs free energy barrier (∆G ‡). It is predicted that the first reaction step consists in the oxidation of Cys263 by H2O2 which is by far the most reactive cysteine (∆G ‡=15.4kcalmol−1). The next two reaction steps are the formation of the first S-S bridge between Cys263 and Cys266 (∆G ‡=13.6kcalmol−1) and the oxidation of Cys231 by H2O2 (∆G ‡=20.4kcalmol−1). It is then shown that the formation of the second S-S bridge (Cys231-Cys233) before the zinc release is most unlikely (∆G ‡=34.8kcalmol−1). Instead, the release of zinc just after the oxidation of the third cysteine (Cys231) is shown to be thermodynamically (dissociation Gibbs free energy ∆G d=6.0kcalmol−1) and kinetically (reaction rate constant k d≈106s−1) favored. This result is in good agreement with the experimental data on the oxidation mechanism of Hsp33 zinc center available to date. SBIC, 2015 Hsp33 nationallicence Redox switch nationallicence Hydrogen peroxide nationallicence Ab initio nationallicence Energy barrier nationallicence Enescu Mironel Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut Kassim Rima Centre de Recherche Universitaire de Djibouti (CRUD), University of Djibouti, Avenue Georges Clemenceau, Djibouti, Djibouti aut Ramseyer Christophe Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut Cardey Bruno Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/3(2015-04-01), 555-562 0949-8257 20:3<555 2015 20 775 https://doi.org/10.1007/s00775-015-1240-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1240-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Enescu Mironel Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut NATIONALLICENCE 700 1- Kassim Rima Centre de Recherche Universitaire de Djibouti (CRUD), University of Djibouti, Avenue Georges Clemenceau, Djibouti, Djibouti aut NATIONALLICENCE 700 1- Ramseyer Christophe Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut NATIONALLICENCE 700 1- Cardey Bruno Laboratoire Chrono Environnement UMR CNRS 6249, University of Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/3(2015-04-01), 555-562 0949-8257 20:3<555 2015 20 775